The present invention relates generally to medicinal compositions and the use thereof; and more particularly, it relates to biologically active peptide compositions useful in the treatment of human neoplastic disease.
Investigations into the presence of physiologically or pathologically active peptides in urine have been on going for the past 80 years. Biologically active polypeptides have been isolated from urine which have demonstrated hormone like activity or regulation of biological function. Examples of biologically active polypeptide compositions isolated from urine include growth factors, pituitary hormones, and kinins.
The practically infinite variety of peptides that can be formed by the combination of the twenty common amino acids has prompted many investigators to suggest that peptides may constitute a system carrying information from cell to cell and organ to organ. Following this view on the regulatory significance of peptides, researchers have isolated urinary peptides which exert an influence on blood pressure, behavior modification, cardiovascular regulation, and smooth muscle activity.
Accordingly, it has been considered by a number of researchers that neoplastic growth may be controlled by naturally occurring biochemical defense mechanisms. The immunological process has most often been attributed with antineoplastic activity (see for example, Aoki et al, Prog. Exp. Tumor Res., 19:23, 1974). There are, however, other possible mechanisms.
It has been suggested that neoplasia is a disease of cell differentiation. Given the large number of differentiating cells and assuming the possibility of error in the program for differentiation, groups of abnormally growing cells can often arise under the influence of carcinogenic factors. Without a reliable mechanism for "normalizing" such erroneously developed cells, the organisms would not live very long. Such a mechanism should be able to correct the growth of newly developed neoplastic cells and direct them into normal differentiation pathways. It is Applicant's belief that peptides are ideal compounds to function as information-carrying molecules regulating cell differentiation.
In recent years, Applicant has described a number of medium-sized peptides derived from human urine, which demonstrate inhibition of DNA synthesis and mitosis in cultures of various neoplastic cells without significant inhibition of normal cells replication [see Burzynski, Physiol. Chem. Phys., 5:437 (1973); Burzynski et al, Fed. Proc., 32:766 (1973); Burzynski et al, Physiol. Chem. Phys. 8:13 (1976); Burzynski et al, Fed. Proc. 35:623 (1976); Gross et al, Physiol. Chem. Phys., 8:161 (1976); Gross et al, Clin. Chem. 23:148 (1977); Burzynski, Physiol. Chem. Phys., 8:275 (1976); and Burzynski et al, Physiol. Chem. Phys. 9:485 (1977)].
The active compounds, but heretofore unidentified discrete compounds, from these fractions have been given the working name "antineoplastons". Applicant has defined antineoplastons as substances produced by a living organism that protect it against development of neoplastic growth by a nonimmunological process which does not significantly inhibit the growth of normal tissues.
Although some polypeptides have been synthesized which demonstrate antineoplastic properties, (see de Barbieri et al, Boll. Chim. Farm., 111:216, 1972), Applicant is not aware of prior art describing small sized (less than 10 amino acids), low-molecular weight polypeptides which have been isolated and identified from tissues or body fluids that exhibit antineoplastic activity significantly higher than inhibition of normal cell growth. Nor is Applicant aware of prior art describing the peptide, 3-[N-phenylacetylaminopiperidine]-2, 6-dion, or its use as an antineoplastic agent.